Infection has become the most serious complication associated with the application of implantable medical devices. Treatment of these infections is difficult and most often necessitates removal of the implanted device. Technological refinements in materials and design and increasing surgical experience has lowered the incidence of infectious complications; however, infection remains a continuing cause of morbidity and mortality.
Approaches to reduce device-related infections initially were focused on improvements of the surgical technique, including modification of the operating room area and the use of prophylactic antibiotics at the time of surgery. Despite the introduction of these meticulous aseptic measures the occurrence of device-related infections could not be completely eliminated.
An alternative approach is to focus on the implant itself, and consequently on modification of the device to enhance infection-resistance by providing surfaces on the device that promote appropriate integration of the surrounding tissue(s) with the device surface. The underlying concept is that when rapid colonization and integration of the device surface with tissue cells is encouraged, the implant surface will be protected from bacterial colonization.
One method of promoting tissue integration is through the use of collagen immobilized on the surface of the device because collagen materials promote a favorable tissue response. They provide a more physiological, isotropic environment that has been shown to promote the organization of different cell types into three-dimensional tissue-like structure. See, for example, Akita et al., Cell Tissue Res., 274, 91-95 (1993); and Berthod et al., Biomaterials, 14, 749-754 (1993). Implant studies have demonstrated that collagen-immobilization promotes favorable integration of tissue(s) with the implanted material. See, for example, Shimizu et al., Biomat., Med. Dev., Artif. Org., 6, 375-391 (1978); Kinoshita et al., Biomaterials, 14, 209-215 (1993); and Okada et al., J. Biomed. Mater. Res., 27, 1509-1518 (1993).
One method of coating synthetic polymers with collagen involves a physical deposition of collagen, such that a laminar material results, as disclosed by Shimizu et al., Biomat., Med. Dev., Artif. Org., 5, 49-66 (1977). One drawback to this method is that the collagen materials are prone to delamination in a moisture-abundant environment such as that typically experienced by implanted medical devices.
Another method of providing a collagen-coated device involves covalently coupling collagen to a synthetic polymer substrate, as disclosed by Okada et al., Biomaterials and Clinical Applications, Elsevier Science Publishers B.V., Amsterdam, The Netherlands, pp. 465-470, 1987. The method includes graft copolymerization of acrylic acid, after which collagen is covalently coupled to the grafted poly(acrylic acid) chains, resulting in a blend-like matrix of collagen and poly(acrylic acid) chains. This construction is schematically depicted in FIG. 1, where the poly(acrylic acid) chains 12 are grafted to the surface 10 of a device. Collagen 14 is contained within the matrix formed by the chains 12. Thus, the collagen is not located primarily at the surface. Thus, biological activity may be reduced as proper expression and accessibility are hampered.